We propose to adopt a very successful approach to "permanent" cardiac allografts in rats to goats to solve problems presented by larger, non-inbred animals. Lethally irradiated rats grafted with allogeneic hearts and repopulated with nonadherent syngeneic marrow and thymus cells after a two-day delay permanently accepted the hearts and were tolerant to donor cardiac tissue. If the cells were infused the day of irradiation and heart transplantation, the grafts were usually promptly rejected. Long-term recipients of cardiac grafts will be grafted with either a donor-type kidney or thyroid graft to determine whether tolerance induction is organ specific. To test for tolerance to donor-type hemopoietic cells the long-term recipients will be irradiated and grafted with allogeneic marrow cells. Five days after cell transfer, we will quantitate cellular proliferation in the spleens as a measure of acceptance or rejection. In order to produce long-term grafts in goats, we propose to remove prospective recipient bone marrow and thoracic duct cells and store them cryogenically. The donor-host degree of incompatibility will be estimated by mixed lymphocyte cultures. The host will be lethally irradiated and grafted heterotopically with a heart on the same day. Autologous hemopoietic cells will be infused either on the same day or two days later. If this approach is successful, orthotopic transplants will be performed.